EFFECTS OF CHRONIC HYPOXIA ON THE PHARMACOKINETICS OF CAFFEINE AND CARDIO-GREEN IN MICRO SWINE

Methods: The pharmacokinetics of caffeine and cardio-green (ICG) were examined in four micro swine at sea level (SEA) and following 21 d con tinuous exposure to 4600 m (ALT) in a hypobaric chamber, Caffeine (84. 7 mg) and ICG(IO mg) were administered as separate intravenous boluses and sequential blood samples collected, Results: Caffeine clearance s ignificantly (p < 0.05) increased in ALT (96.8 +/- 20.0 ml min(-1)) as compared to SEA (53.6 a 24.8 ml min(-1)), demonstrating that liver fu nction increased in ALT, There was no significant change in the ratio of primary metabolites to caffeine, suggesting that the increase in cl earance was not due to a change in the rate of caffeine metabolism. IC G clearance significantly increased in ALT (179.8 a 57.4 ml min(-1)) a s compared to SEA (84.4 +/- 28.9 ml min(-1)) indicating that hepatic b lood flow (HBF) increased. Conclusion: These results demonstrate that chronic exposure to 4600 m increases the clearance of caffeine and ICG in the micro swine model and suggests that the increase in caffeine c learance is related to HBF.